Short Stereoselective Route to γ-CF3 Allylic Alcohols: Rearrangements with Creation of Quaternary CF3-Substituted Carbons

Article abstract of DOI:10.1021/jo991702d

A concise preparation of tetrasubstituted hindered functionalized CF₃-olefins 2-7 from corresponding enol ether 3 is described. Geometrically pure γ-CF₃,γ-alkyl allylic alcohols thus prepared could undergo Claisen-type rearrangements and provide, in good yields, carboxylic esters and amides containing a β- quaternary CF₃-substituted carbon.

Full text of DOI:10.1021/jo991702d

2104
J . Org. Chem. 2000, 65, 2104-2107
Sh or t Ster eoselective Rou te to γ-CF 3 Allylic Alcoh ols:
Rea r r a n gem en ts w ith Cr ea tion of Qu a ter n a r y CF 3-Su bstitu ted
Ca r bon s
Denis Bouvet,† Hamid Sdassi,‡ Miche`le Oure´vitch,† and Danie`le Bonnet-Delpon*,†
BioCIS, UPRES A-8076. Centre d’Etudes Pharmaceutiques, Rue J -B Cle´ment,
92296 Chaˆtenay-Malabry, France, and Universite´ Chouaib Doukkali, Faculte´ des Sciences,
El J adida, Morocco
Received October 29, 1999
A concise preparation of tetrasubstituted hindered functionalized CF3-olefins 2-7 from correspond-
ing enol ether 3 is described. Geometrically pure γ-CF3,γ-alkyl allylic alcohols thus prepared could
undergo Claisen-type rearrangements and provide, in good yields, carboxylic esters and amides
containing a â- quaternary CF3-substituted carbon.
Sch em e 1
Claisen rearrangement and its variants found applica-
tions in the synthesis of trifluoromethylated compounds.
Allyl vinyl ethers and allyl ketene silyl acetals, substi-
tuted with a trifluoromethyl group in the vinyl segment,
readily undergo Claisen rearrangements and provide a
good access to ramified trifluoromethyl ketones and
R-CF3 unsaturated acids, respectively.1 γ-CF3-allylic al-
cohols can be involved in Claisen,2 J ohnson-Claisen,3
Eschenmoser-Claisen,3 and Ireland-Claisen4 rearrange-
ments, which allowed the generation of secondary car-
bons, substituted with a trifluoromethyl group and a â
functionality. To our knowledge, this potent tool has
generally not been used to generate quaternary CF3-
substituted carbons, probably due to a lack of easy access
to geometrically pure γ-CF3, γ-alkyl allylic alcohols.5 The
Wittig condensation of trifluoromethyl ketones or tri-
fluoroacetic anhydride with carbethoxy phosphoranes,
leading to the corresponding R,â-unsaturated esters, is
generally nonstereoselective.6 Unlike the reduction of
γ-CF3 propargylic alcohols7, other addition reactions to
CF3-substituted acetylenic compounds are poorly selec-
tive and have not been developed for the preparation of
highly substituted allylic alcohols.8 An alternative route
to γ-CF3 allylic alcohols is the trapping, with an electro-
philic carbonyl compound, of â-metalated CF3-substituted
olefins. However, very little has been reported on this
approach and no example concerns R,R-disubstituted
olefins.9 We have published as a preliminary result that
the olefin 1a could be metalated and react with propanal
to give the allylic alcohol 2a (Scheme 1).10 We report here
the development of this approach for a stereoselective
access to functionalized hindered (trifluoromethyl)al-
kenes and Claisen-type rearrangements of thus prepared
γ,γ-disubstituted allylic alcohols 2.
Resu lts a n d Discu ssion
P r ep a r a tion of Allylic Alcoh ols 2a -c a n d 4a -c
a n d Alk en es 6a a n d 7b. As previously reported, 1a was
found to react at room temperature with tert-butyllithium
reagent (t-BuLi) in the presence of N,N,N′,N′-tetrameth-
ylenediamine (TMEDA) in hexane, and the resulting
vinyl anion could be quenched with propanal, providing
the allylic alcohol 2a .10 Since trisubstituted CF3-olefins
(E)-1 were themselves stereoselectively prepared from the
enol ether (Z)-3, through a carbolithiation-elimination
reaction performed at -78 °C with alkyllithium reagents
in tetrahydrofuran (THF) (Scheme 2),10 we envisaged a
one-pot stereoselective preparation of allylic alcohols from
3.
† BioCIS.
‡ Universite´ Chouaib Doukkali.
(1) Krespan, C. G. Tetrahedron 1967, 23, 4243-4249. (b) Yokozawa,
T.; Nakai, T.; Ishikawa, N. Tetrahedron Lett. 1984, 25, 3991-3994.
(c) Gajewski, J . J .; Gee, K. R.; J urayj, J . J . Org. Chem. 1990, 55, 1813-
1822. (d) Be´gue´, J . P.; Bonnet-Delpon, D.; Wu, S. W.; M’Bida, A.;
Shintani, T.; Nakai, T. Tetrahedron Lett. 1994, 35, 2907-2910.
(2) Yamazaki, T.; Ishikawa, N. Bull. Soc Chem. Fr. 1986, 937-943.
(3) Hanzawa, Y.; Kawagoe, K.; Yamada, A.; Kobayashi, Y. Tetra-
hedron Lett. 1985, 26, 219-222. (b) Konno, T.; Nakano, H.; Kitazume,
T. J . Fluorine Chem. 1997, 86, 81-87.
(4) Konno, T.; Umetani, H.; Kitazume, T. J . Org. Chem. 1997, 62,
137-150
(5) One example of Claisen rearrangement is described from the
â-CF3, â-CH3 allylic alcohol: Haddad, M.; Molines, H.; Wakselman,
C. Synthesis 1994, 167-169.
(6) Camps, F.; Canela, R.; Coll, J .; Messeguer, A.; Roca, A. Tetra-
hedron 1978, 34, 2179-2182. (b) A.Shen, Y.; Xiang, Y. J . Fluorine
Chem. 1991, 52, 221-227. (c) Martin V.; Molines, H.; Wakselman, C.
J . Fluorine Chem. 1993, 62, 63-68.
(7) Hanzawa, Y.; Kawagoe, K.; Tanahashi, N.; Kobayashi, Y.
Tetrahedron Lett. 1984, 25, 4749-4752. (b) Yamazaki, T.; Mizutani,
K.; Kitazume, T. J . Org. Chem. 1995, 60, 6046-6056.
(8) For some reports on addition to trifluoromethyl acetylenic
compounds, see: (a) Poulter, C. D.; Wiggins, P. L.; Plummer, T. L. J .
Org. Chem. 1981, 46, 1532-1538. (b) Bumgardner, C. L.; Bunch, J .
E.; Whangbo, M.-H. J . Org. Chem. 1986, 51, 4083-4085. (c) Lawate,
S. S.; Covey, D. F. J . Med. Chem. 1990, 33, 2321-2323.
We first checked that the carbolithiation-elimination
reaction could occur at room temperature in hexane in
the presence of TMEDA, which are the conditions of the
metalation step. At room temperature, 1 equiv of t-BuLi
reacted instantaneously with the enol ether 3 to provide
(9) Yamazaki, T.; Takita, K.; Ishikawa, N. J . Fluorine Chem. 1985,
30, 357. (b) Taguchi, T.; Tomizawa, T.; Kawara, A.; Nakajima, M.;
Kobayashi, Y. J . Fluorine Chem. 1988, 40, 171-182.
(10) Be´gue´, J -P.; Bonnet-Delpon, D.; Bouvet, D.; Rock, M. H. J . Org.
Chem. 1996, 61, 9111-9114.
10.1021/jo991702d CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/11/2000

Stereoselective Route to γ-CF3 Allylic Alcohols
J . Org. Chem., Vol. 65, No. 7, 2000 2105
Ta ble 1. On e-P ot Rea ction of Vin yl Eth er 3 w ith
Or ga n olith iu m Rea gen ts a n d Tr a p p in g w ith
Electr op h iles
Sch em e 2
Sch em e 3
quantitatively the alkene (E)-1a . This confirms that, even
under these new conditions, the deprotonation of 3 is not
competitive with the carbolithiation reaction. The enol
ether 3 was then treated with 2.1 equiv of tert-butyl-
lithium, at room temperature in hexane in the presence
of 2.1 equiv of TMEDA, and 1.2 equiv of propanal was
added to the red solution of vinyl anion. After 1 h, the
allylic alcohol 2a was obtained, accompanied by alkene
1a (about 80/20). An excess of base and aldehyde had only
a slight influence on the course of the reaction, but the
yield of 2a was highly dependent on the time between
addition of the organolithium reagent and that of alde-
hyde. A time of 7 min before the addition of the aldehyde
appeared to be the best compromise to allow for the
optimal formation of the vinyl anion and its trapping.
Under these conditions, (Z)-2a could be obtained in 75%
yield (Scheme 3, Table 1). This one-pot reaction was then
extended to other organolithium reagents and to other
electrophiles. We already knew that lithium amides could
not be used in this reaction since they react with enol
ether 3 to give corresponding enamines and do not allow
the deprotonation of these latter.11 Reaction of 3 with
n-butyllithium or sec-butyllithium reagents and quench-
ing, after 7 min, with propanal provided alcohols 2b and
2c in 83% and 82% yields, respectively, 2c being a 50/50
mixture of two diastereoisomers (Scheme 3, Table 1).
However, when the reaction was performed with meth-
yllithium (MeLi), the only isolated compound was the
olefin 1d , indicating that MeLi is not a strong enough
base to allow the metalation step.12 When generated,
vinyl anions could also be trapped with benzaldehyde and
acetaldehyde, leading to alcohols 4a -c and 5b in excel-
lent yields. Ethyl chloroformate and dimethyl sulfide
could also act as electrophiles, providing the R-â unsatur-
ated ester 6a (R ) t-Bu) and the vinyl sulfide 7b (R )
n-Bu) (Table 1).
a
Isolated yield.
configuration of the double bond. Furthermore, 13C NMR
spectra of all allylic alcohols exhibit a J CF coupling
4
constant for the C(OH) carbon, indicating a proximity
between the two nucleii. The stereochemistry was not
unambiguously demonstrated for 6a and 7b.
Rea r r a n gem en ts of Allylic Alcoh ols. (Z)-Allylic
alcohols 2-5, prepared as mentioned above, were sub-
jected to ortho ester J ohnson-Claisen and Eschen-
moser-Claisen rearrangements.
For the ortho ester rearrangement, reactions were
conducted under conditions similar to that reported by
J ohnson13 (an excess amount of methyl orthoacetate with
5 mol % of propionic acid heated to 120 °C). From 2b,
4b, and 5b, rearranged â-CF3 esters 8, 9, and 10 could
be obtained, accompanied by a 10-20% mixture of
starting allylic alcohol and other unidentified CF3-
substituted ethylenic compounds (according to their 19F
NMR chemical shifts). A higher temperature of reaction
did not improve yields in esters. After purification, 8, 9,
and 10 could be isolated in 80%, 68%, and 75% yields,
respectively (Scheme 4). The E configuration of the newly
formed carbon-carbon double bond was demonstrated by
NMR experiments. After complete assignment as de-
scribed above, homo- and heteronuclear Overhauser
effects allow to identify the proximity of the ethylenic
proton with other atoms: in 8, with CF3 and both
methylene groups adjacent to the quaternary center; in
All compounds were stereoselectively obtained. The Z
configuration of the double bond in 4c was demonstrated
by NOE experiments. After complete assignment of
protons by COSY heteronuclear multiple-quantum coher-
ence (HMQC), and heteronuclear multiple bond coher-
ence (HMBC), irradiation of fluorine atoms resulted in a
7% enhancement of the signal of the proton geminal to
the hydroxy group. This effect indicates a spatial proxim-
ity of CF3 and CHOH groups and demonstrates the Z
(11) Be´gue´, J -P.; Bonnet-Delpon, D.; Rock, M. H. J . Chem. Soc.,
Perkin Trans. 1 1996, 1409-1413.
(12) When 1d was treated with BuLi, an undetermined mixture was
obtained.
(13) J ohnson, W. S.; Wetheman, L.; Bartlett, W. R.; Brockson, T.
R.; Li, T.; Faulkner, D. J .; Petersen, M. R. J . Am. Chem. Soc. 1970,
92, 741.

2106 J . Org. Chem., Vol. 65, No. 7, 2000
Bouveta et al.
of ammonium chloride. Organic phases were extracted with
dichloromethane (3 × 20 mL), dried (MgSO4), and evaporated
to give a pale yellow oil that was purified by chromatography
on silica gel (eluent: pentane/ether 90/10) to the pure com-
pound.
Sch em e 4
(Z)-2,2-Dim eth yl-5-h yd r oxy-4-p h en yl-3-tr iflu or om eth -
ylh ep t-3-en e (2a ). A solution of enol ether 3 (220 mg, 1 mmol),
tert-butyllithium (1.4 mL of a 1.5 M solution in hexanes, 2.1
mmol), TMEDA (490 mg, 2.1 mmol) in hexane (10 mL), after
addition of propanal (70 mg, 1.2 mmol), afforded, after workup
and purification, the alcohol 2a (210 mg, 75%): IR (CCl4) 3640,
1
1635 cm-1
;
19F NMR δ -48.9 (s); H NMR δ 0.8 (t, J ) 7 Hz,
CH3), 0.9 (s, 9 H), 1.5 (m, 2 H, CH2), 4.6 (m, 1 H, CHOH), 6.9-
Sch em e 5
7.2 (m, 5 H, C6H5); 13C NMR δ 10.2, 28.9, 31.5, 37.2, 73.1 (q,
1
4J CF ) 4.6 Hz, CHOH), 125.5 (q, J CF ) 282 Hz, CF3), 126.9,
2
127.0, 127.1, 129.7, 130.6, 135.2 (q, J CF ) 23.5 Hz, CCF3),
3
136.6, 149.2 (q, J CF ) 2.9 Hz, CdCCF3). Anal. Calcd for
C
16H21F3O: C, 67.13; H, 7.34. Found: C, 67.30; H, 7.35
(Z)-3-H yd r oxy-4-p h en yl-5-t r iflu or om et h yln on -4-en e
(2b). A solution of enol ether 3 (220 mg, 1 mmol), n-
butyllithium (1.3 mL of a 1.6 M solution in hexanes, 2.1 mmol),
and TMEDA (490 mg, 2.1 mmol) in hexane (10 mL), after
addition of propanal (70 mg, 1.2 mmol), afforded, after workup
and purification, the alcohol 2b (232 mg, 83%): 19F NMR δ
1
9, with CF3; in 10, with methylene groups. In all cases,
no traces of the Z isomer could be detected. This revealed
that the rearrangement only proceeded via the sterically
less hindered six-membered ring transition state, where
the R′ substituent (Me, Et, or Ph) occupies the equatorial
position. In previously described similar rearrangements,
this isomer is always predominant but not the sole
product.2,3b
The allylic alcohol 4b could also undergo rearrange-
ment after exposure to an amide acetal. According to
literature conditions,14 in the presence of an excess of
1-(dimethylamino)-1,1-dimethoxyethane and an equal
volume of dry diglyme, at 160 °C, 4b provided the amide
11 (75%) as a single stereoisomer at the newly created
olefinic bond (Scheme 5). The E configuration was as-
signed as described for 8-10.
-55.7 (s); H NMR δ 0.71 (t, J ) 7 Hz, 3 H), 0.93 (d, J ) 7.4
Hz, 3 H), 1.0-1.4 (m, 8 H), 1.6 (broad s, 1 H, OH), 4.75 (m, 1
H), 7.2 (m, 5 H, C6H5); 13C NMR δ 10.3, 13.5, 22.5, 28.7, 29.5,
4
1
31.4, 71.8 (q, J ) 2.6 Hz), 124.8 (q, J ) 278 Hz, CF3), 127.6,
2
128.1, 129.0, 130.2 (q, J CF ) 28 Hz, C-CF3), 135.9, 149.6.
Anal. Calcd For C16H21F3O: C, 67.13; H, 7.34. Found: C, 66.79;
H, 7.66.
(Z)-3-Hydr oxy-6-m eth yl-4-ph en yl-5-tr iflu or om eth yloct-
4-en e (2c). A solution of enol ether 3 (220 mg, 1 mmol), sec-
butyllithium (1.6 mL of a 1.5 M solution in hexanes, 2.1 mmol),
and TMEDA (490 mg, 2.1 mmol) in hexane (10 mL), after
addition of propanal (70 mg, 1.2 mmol), afforded, after workup
and purification, the alcohol 2c (232 mg, 82%): IR (neat) 3450,
1630 cm-1 19F NMR δ -52.0 (s); 1H NMR δ 0.65 (t, J ) 7 Hz)
;
and 0.7 (t, J ) 7 Hz) (CH3), 0.9 (m, J ) 7. Hz, 6 H), 1.40 (m,
4 H), 2.20 (m, CH(CH3)), 4.7 (m, CHOH), 7.2 (m, 5H); 13C NMR
δ 10.1/10.2, 12.4/12.5, 18.3/18.9, 27.1/27.3, 27.9, 38.1, 71.8 (q,
1
4J CF ) 2.7 Hz), 125.0 (q, J CF ) 292 Hz, CF3), 127.4, 127.7,
127.9, 128.2, 128.3, 129.4, 132.8 (m, CCF3), 136.1/136.6, 150.0
(q, 3J CF ) 5.5 Hz). Anal. Calcd for C16H21F3O: C, 67.13; H, 7.34.
Found: C, 67.25; H, 7.33.
(Z)-4,4-Dim et h yl-1,2-d ip h en yl-1-h yd r oxy-3-t r iflu or o-
m eth ylp en t-2-en e (4a ). A solution of enol ether 3 (220 mg, 1
mmol), tert-butyllithium (1.4 mL of a 1.5 M solution in
hexanes, 2.1 mmol), and TMEDA (490 mg, 2.1 mmol) in hexane
(10 mL), after addition of benzaldehyde (132 mg, 1.2 mmol),
afforded, after workup and purification, the alcohol 4a (320
mg, 95%).
We have described a short and effective access to
functionalized and sterically hindered CF3-substituted
alkenes in two steps from trifluoroacetic esters. This
method allowed the access to geometrically pure γ-CF3,
γ-alkyl allylic alcohols. When treated with an ortho ester
or with an amide acetal, they easily rearranged into ester
or amide with creation of a CF3-substituted quaternary
carbon and a stereoselective formation of new double
bond.
(Z)-1,2-Dip h en yl-1-h yd r oxy-3-t r iflu or om et h ylh ep t -2-
en e (4b). A solution of enol ether 3 (220 mg, 1 mmol),
n-butyllithium (1.3 mL of a 1.6 M solution in hexanes, 2.1
mmol), and TMEDA (490 mg, 2.1 mmol) in hexane (10 mL),
after addition of benzaldehyde (132 mg, 1.2 mmol), afforded,
after workup and purification, the alcohol 4b (238 mg, 83%).
(Z)-1,2-Dip h en yl-1-h yd r oxy-4-m eth yl-3-tr iflu or om eth -
ylh ex-4-en e (4c). A solution of enol ether 3 (220 mg, 1 mmol),
sec-butyllithium (1.6 mL of a 1.5 M solution in hexanes, 2.1
mmol), and TMEDA (490 mg, 2.1 mmol) in hexane (10 mL),
after addition of benzaldehyde (132 mg, 1.2 mmol), afforded,
after workup and purification, the alcohol 4c (298 mg, 88%).
(Z)-2-Hydr oxy-3-ph en yl-4-tr iflu or om eth yl-oct-3-en e (5b).
A solution of enol ether 3 (1 g, 4.6 mmol), n-butyllithium (6.1
mL of a 1.6 M solution in hexanes, 2.1 mmol), and TMEDA
(2.254 g, 2.1 mmol) in hexane (40 mL), after addition of
acetaldehyde (660 µL, 11.6 mmol), afforded, after workup and
purification, the alcohol 5b (1.1 g, 88%).
Exp er im en ta l Section
Alkenes 1 were already described.10 Enol ether 3 was
prepared from ethyl trifluoroacetate.15
Elemental analyses were performed by the Service de
Microanalyses of the Centre d′Etudes Pharmaceutiques, Chaˆt-
enay-Malabry. All the reactions were performed in an oven-
dried apparatus under an inert atmosphere of argon. Com-
mercial reagents were used without further purification.
Gen er a l P r oced u r e for th e P r ep a r a tion of Alk en es 2,
4, 5, 6, a n d 7. A solution of enol ether 3 (1 equiv) and TMEDA
(2.1 equiv) in hexane was treated under argon with 2.1 equiv
of alkyllithium at room temperature. A red color appeared,
and after 7 min of stirring, 1.2 equiv of the electrophilic
compound (propanal, benzaldehyde, ethyl chloroformate, di-
methyldisulfure) (2.5 equiv for acetaldehyde) was introduced.
After 1 h, the mixture was treated with a saturated solution
Eth yl (Z)-4,4-Dim eth yl-2-p h en yl-3-tr iflu or om eth ylp en -
ten oa te (6a ). A solution of enol ether 2 (220 mg, 1 mmol),
tert-butyllithium (1.4 mL of a 1.5 M solution in hexanes, 2.1
mmol), and TMEDA (490 mg, 2.1 mmol) in hexane (10 mL),
after addition of ethyl chloroformate (132 mg, 1.2 mmol),
(14) Wick, A. E.; Felix, D.; Steen, K.; Eschenmoser, A. Helv. Chim.
Acta 1964, 47, 2425.
(15) Be´gue´, J -P.; Bonnet-Delpon, D.; Mesureur, D.; Ne´e, G.; Wu,
S., W. J . Org. Chem. 1992, 57, 3807-3814.

Stereoselective Route to γ-CF3 Allylic Alcohols
J . Org. Chem., Vol. 65, No. 7, 2000 2107
afforded, after workup and purification and purification, the
136.8, 138.6, 170.5 (CdO). Anal. Calcd For C19H25F3O2: C,
66.65; H, 7.36. Found: C, 66.52; H, 7.54.
ester 6a (242 mg, 79%): IR (neat) 1730, 1630 cm-1
;
19F NMR
1
δ -55.6 (s); H NMR δ 1.0 (s, 9 H), 1.20 (t, J ) 7.1 Hz, 3 H),
Meth yl (Z)-3-Bu tyl-3-tr iflu or om eth yl-4,5-diph en ylpen t-
4-en oa te (9). From 4b (0.6 mmol, 200 mg) and methyl
orthoacetate (1.1 mmol, 0.8 mL), reaction and workup afforded,
after purification, the pure compound 9 as a colorless liquid
(160 mg, 68%).
Meth yl (E)-3-Bu tyl-3-tr iflu or om eth yl-4-p h en ylh ex-4-
en oa te (10). From 5b, (1.1 mmol, 300 mg), and methyl
orthoacetate (1.1 mmol, 1.4 mL), reaction and workup afforded,
after purification, the pure compound 10 as a colorless liquid
(258 mg, 75%).
4.05 (q, J ) 7.1 Hz, 2 H), 7.2 (m, 5 H); 13C NMR δ 14.0, 29.5,
1
36.0, 61.5, 124.5 (q, J CF ) 280 Hz, CF3), 127.0, 128.2, 128.3,
2
3
130.2, 135.2 (q, J CF ) 25.5 Hz, CCF3), 136.0, 141.0 (q, J CF
)
4.7 Hz CdCCF3), 168.2 (CO). Anal. Calcd for C16H19F3O2: C,
64.00; H, 6.33. Found: C, 64.09; H, 6.50.
(Z)-1-P h e n yl-1-t h iom e t h yl-2-t r iflu or om e t h ylh e x-1-
en e (7b). A solution of enol ether 2 (220 mg, 1 mmol),
n-butyllithium (1.3 mL of a 1.6 M solution in hexanes, 2.1
mmol), and TMEDA (490 mg, 2.1 mmol) in hexane (10 mL),
after addition of dimethyl disulfide (108 mg, 1.2 mmol),
afforded, after workup and purification, 7b (204 mg, 75%): IR
Rea r r a n gem en t of Esch en m oser -Cla isen : P r ep a r a -
tion of Meth yl (E)-3-Bu tyl-3-tr iflu or om eth yl-4,5-d ip h en -
ylp en t-4-en e-(N,N-d im eth yl)a m id e (11). A mixture of the
allylic alcohol 4b (300 mg, 0.9 mmol) and N,N-dimethylacet-
amide (1 mL) in dry diglyme (1 mL) was heated in a 25 mL
flask fitted with a variable takeoff distilling head. The distil-
late was removed at a vapor temperature of 160 °C, and after
2 h of additional heating, the solvent was removed under
pressure. The yellow oil was purified by chromatography on
silica gel (eluent: petroleum ether/EtOAc 95/5) to give the pure
compound 11, as a colorless oil (260 mg, 75%): 19F NMR δ
(neat) 1665 cm-1 19F NMR δ -59.1 (s); 1H NMR δ 0.65 (t, J )
;
6.7 Hz, 3 H), 1.0 (m, 2 H), 1.25 (m, 2 H), 1.65 (s, CH3S), 1.95
(t, J ) 7.3 Hz, 2 H), 7.2 (m, 5H); 13C NMR δ: 13.6, 15.7, 22.5,
1
2
30.7, 31.8, 124.5 (q, J CF ) 278.7 Hz, CF3), 128.1 (q, J CF ) 32
Hz, CdCF3), 128.4, 128.6, 128.7, 137.1, 144.8. Anal. Calcd for
C11H17SF3: C, 55.46; H, 7.14. Found: C, 55.40; H, 6.98.
J oh n son -Cla isen Rea r r a n gem en t of Allylic Alcoh ols
2b, 4b, a n d 5b: Gen er a l P r oced u r e. A mixture of allylic
alcohol, methyl orthoacetate (∼10 equiv), and a catalytic
amount of propionic acid (1 drop) was heated in a flask at a
vapor temperature of 110-120 °C until methanol no longer
distilled from the reaction flask (about 1 h). After cooling,
volatile material was removed under reduced pressure, and
the crude product was purified by chromatography on a silica
gel column (eluent: petroleum ether/ethyl acetate mixture 95/
5).
1
-71.1 (s); H NMR δ.0.91 (t, J ) 7.2 Hz, 3 H), 1.35 (m, 3 H),
2
3
3
1.5 (m, 1 H), 2.12 (ddd, J ) 14 Hz, J ) 11 Hz J ) 4 Hz, 1
2
3
3
H), 2.35 (td, J ) J ) 14 Hz J ) 4 Hz, 1 H), 2.65 and 2.70
2
(2d, J ) 16 Hz, 2 H), 2.85 (s, 6 H), 6.8 (s, 1 H, CdCH), 7.05
(m, 10 H); 13C NMR δ 14.0, 23.2, 27.0, 32.5, 32.9, 35.6, 37.5,
51.3 (q, 2J CF ) 22 Hz, C-CF3), 126.8, 127.2, 127.7, 128.1, 128.5
(q, 1J CF ) 285 Hz, CF3), 129.4, 130.6, 132.2, 136.7, 138.9, 140.2,
169.1 (CdO). Anal. Calcd for C24H28F3NO: C, 71.16; H, 6.99;
N, 3.47. Found: C, 71.16; H, 7.19; N, 3.08.
Meth yl (E)-3-Bu tyl-3-tr iflu or om eth yl-4-p h en ylh ep t-4-
en oa te (8). From 2b, (1.05 mmol, 300 mg), and methyl
orthoacetate (1.1 mmol, 1.4 mL), reaction and workup afforded,
after purification, the pure compound 8 as a colorless liquid
Ack n ow led gm en t. H.S. thanks the Centre d’e´tudes
Pharmaceutiques (University Paris-XI) for a position of
invited Professor.
1
(273 mg, 80%): 19F NMR δ -71.2 (s); H NMR δ 0.85 (t, J )
7.4 Hz, 3 H), 0.89 (t, J ) 7.2 Hz, 3 H), 1.30-1.45 (m, 4 H),
1.66 (quint, J ) 7.4 Hz, 2 H), 1.9 (m, 2 H), 2.56 and 2.64 (2d,
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic and
analytical data for 4b,c, 5b, 6a -c, 9, and 10. This material is
available free of charge via the Internet at http:/pubs.acs.org.
3
5
2J ) 15.3 Hz, 2 H), 3.6 (s, 3 H), 5.87 (tq, J ) 7.4 Hz, J HF
)
0.9 Hz, 1 H, CdCH), 7.15 (m, 5 H, C6H5); 13C NMR δ 13.7,
13.9, 23.1, 26.2, 31.6, 36.1, 50.5 (q, 2J CF ) 23 Hz, C-CF3), 51.5,
126.9, 127.8, 127.9 (q, 1J CF ) 278 Hz, CF3), 129.8, 129.9, 135.9,
J O991702D